Cardiovascular disease, including atherosclerosis, is a leading cause of death in the U.S. A number of methods and devices for treating coronary heart disease have been developed, some of which are specifically designed to treat the complications resulting from atherosclerosis and other forms of coronary arterial narrowing.
One method of treating atherosclerosis and other forms of coronary narrowing is percutaneous transluminal coronary angioplasty, hereinafter referred to as “angioplasty” or “PTCA”. Many heart disease patients undergo angioplasty, some repeatedly.
The objective of angioplasty is to enlarge the lumen of the affected coronary artery by radial hydraulic expansion. This is generally accomplished by inflating a balloon within the narrowed lumen of the affected artery. Radial expansion of the coronary artery may occur in several different dimensions, and is related to the nature of the plaque. Soft, fatty plaque deposits are flattened by the balloon, while hardened deposits are cracked and split to enlarge the lumen. The wall of the artery itself may also be stretched as the balloon is inflated.
With simple angioplasty, the balloon is threaded through the artery with a catheter and inflated at the place where the blood vessel is blocked. After the procedure, the balloon is removed. Following simple angioplasty alone, arteries frequently close up again or re-narrow. This re-narrowing is known as restenosis.
To reduce the risk of restenosis, a stent may be inserted during angioplasty. The stent may be used to support plaque damaged arterial walls and maintain the internal lumen of the artery after a blockage has been removed. The use of a stent may significantly reduce the risk of restenosis, but it does not eliminate it.
Blood vessel wall injury when the stent is implanted is, in fact, one cause of restenosis. The area around the stent becomes inflamed and new cells form scar tissue. The arterial walls may become so thick that, in some instances, they protrude into the mesh of the stent. In such cases, another angioplasty procedure may be performed, and a new stent may be placed inside the existing one.
One means of reducing the incidence of restenosis is delivering a drug at the angioplasty site. Drug coated stents have been used for this purpose. The stent may be coated, for example, with rapamycin analogs or rapamycin derivatives. This drug is used to prevent organ rejection in kidney transplants. It stops new cells from forming without impairing the healing of the vessel. It also dampens inflammation and has antibiotic properties. In clinical studies, patients who received stents coated with rapamycin analogs or rapamycin derivatives exhibited a substantially reduced re-narrowing and re-blockage of treated arteries.
Another means of reducing restenosis is by delivering a therapeutic agent directly to the treatment site during the angioplasty procedure. For example, U.S. Pat. No. 5,087,244 describes a catheter with an expandable balloon near its distal tip. The balloon is filled with the therapeutic agent to be delivered, and expands until it contacts the vessel wall. The therapeutic agent flows out of the balloon through holes in the balloon surface and bathes the vessel wall.
U.S. Pat. No. 6,544,223 describes an inflatable balloon having a plurality of holes through the surface of the balloon. A microporous coating covers at least a portion of the outer surface of the balloon. The thickness of the coating and the size of the micropores permit controlled delivery of a therapeutic substance to the vessel wall.
U.S. Pat. No. 5,112,305 describes a catheter with an expandable balloon. Disposed about the outer surface of the balloon are a plurality of tubular extensions. The balloon is placed at a treatment site, and a therapeutic agent is used to expand the balloon abruptly, causing the tubular extensions to puncture the vessel wall, and deliver the therapeutic agent into the vessel wall.
U.S. Pat. No. 6,409,716 discloses a catheter with an expandable member near the distal end of the catheter. At least a portion of the expandable member is coated with a swellable hydrogel polymer. Incorporated in the hydrogel polymer is an aqueous solution of a drug that is to be delivered to the tissue. The drug is released during compression of the hydrogel polymer coating against the wall of the vessel when the expandable member is expanded.
Although all of these systems provide a means for delivering a therapeutic agent to a localized site on a vessel wall, they require an expandable balloon, which occludes blood flow through the vessel during delivery of the therapeutic agent and prevents perfusion of tissue downstream from the treatment site. Consequently, such devices can usually be deployed for only a few minutes, limiting the amount of the therapeutic agent that can be delivered.
U.S. Pat. No. 5,279,565 discloses a catheter with a movable support frame near the distal end of the catheter. The support frame is operated by an actuator shaft and moves between a retracted position adjacent to the catheter body and a deployed position radially extended from the catheter body. On the external surface of the support frame is a rigid platform having a radially-facing contact surface with a delivery interface for delivering the therapeutic agent. The delivery interface may be a porous rigid matrix, a manifold of tubes with radially-facing perforations, a bladder having a plurality of perforations on its radially-facing surface or a detachable porous membrane for applying a cell graft to the treatment site. Although this device allows blood to flow freely while it is deployed, it applies the therapeutic agent only to the surface of the treatment site.
It would be desirable therefore, to provide a device and method of delivering a therapeutic agent to a treatment site within the vascular system that would overcome these and other limitations while delivering the therapeutic agent to a defined depth within the vascular tissue.